Adding a fullness hormone to a weekly shot led to more weight loss at the top dose in a mid-stage trial

In Short. Tirzepatide, a weekly shot for weight and blood sugar, copies two gut hormones. Lilly has added a third signal, amylin, a hormone that helps you feel full after a meal. In a 48-week mid-stage trial in people with obesity and type 2 diabetes, the highest-dose pair lost more weight than tirzepatide alone, though more people on the combinations than on tirzepatide alone stopped over side effects, and the trial cannot show how a finished product will do.

MANY PEOPLE WITH OBESITY ALSO HAVE type 2 diabetes, a disease in which blood sugar runs too high, and lasting weight loss has been difficult for them, according to the European Association for the Study of Diabetes (EASD). A trial from Eli Lilly asked whether adding one more hormone signal to a drug people already use could move weight and blood sugar further.

First, the disease. In type 2 diabetes the body does not make enough insulin, a hormone from the pancreas that helps sugar move from the blood into cells, or does not use it well. Too much sugar stays in the blood. Doctors track it with A1C, a blood test that reflects average blood sugar over about three months.

Eating sets off hormones, chemical messengers carried in the blood. Two come from the gut, GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1). A third, amylin, comes from the pancreas, where the cells that make insulin release it alongside insulin. Each acts through its own receptor, a detector protein on cells, to help regulate hunger and blood sugar. Reviews describe amylin as slowing the emptying of the stomach, acting on parts of the brain that signal fullness, and restraining glucagon, a hormone that prompts the liver to release sugar.

Tirzepatide, sold as Zepbound and Mounjaro, is a weekly injection that copies GIP and GLP-1. Eloralintide, also weekly, copies amylin only. Lilly calls the two together EloraTZP. A Lilly executive said the pairing "could be an additive and more physiological approach." A 2025 review in Diabetes Therapy says GLP-1 and amylin act through both distinct and overlapping brain pathways for fullness and reward.

This was a phase 2b trial, a middle-stage test of doses before the large final trials. It randomly assigned 367 adults with obesity or overweight and type 2 diabetes to one of ten groups. Lilly, which makes both drugs, paid for it. Neither participants nor investigators knew who got what (double-blind). Groups received a placebo (a dummy injection), eloralintide alone, tirzepatide alone at 15 mg, or both drugs at several doses as two separate injections, with doses rising every four weeks. The tirzepatide-only group matters most, since it is a drug people already get, not only a dummy. The registry lists it as the active comparator. It is one group among ten in a dose-finding trial, not a large head-to-head test built to prove superiority. Lilly's results table lists nine of the ten groups, and neither its release nor the registry gives a head count per group.

Each figure below answers one question, which trial statisticians call the estimand. Lilly reports the "efficacy estimand," which counts people as if they had stayed on treatment for all 48 weeks. It shows what the drug can do when taken, not what happens to everyone assigned to it. Lilly's release gives no figures for that second question.

On that basis, people on the highest combination (eloralintide 9 mg plus tirzepatide 15 mg) lost an average 23.3% of body weight, and their A1C fell 2.9 percentage points from an average start of 8.1%. On tirzepatide 15 mg alone the figures were 14.8% and 2.4 points. On placebo they were 3.0% and 0.3 points. Lilly says eloralintide alone lost 8.2% to 12.3% across its doses. Three combinations with less drug lost 13.2% to 19.9%, and the lowest was below tirzepatide alone. The release gives no statistical test against tirzepatide alone, so this article makes no claim of significance.

The most common side effects were stomach and bowel problems, mostly mild or moderate and mostly during dose increases. Lilly says they were more frequent with the combinations. It reports that 10.8% to 27.0% of people on combinations stopped over side effects, against 2.9% on tirzepatide alone, 0% to 10.8% on eloralintide alone and 16.7% on placebo. A table for each combination was not found, and the registry has posted no results.

Some questions are open. The release does not say how much of the extra loss comes from amylin itself and how much from a larger total dose of drug. It covers 48 weeks, so it cannot show whether weight stays off or the longer-term safety. Lilly says it plans to start phase 3 trials of a single combined product by the end of 2026.

This is a real mid-stage result against a drug people already use, not a finished product, and it does not settle how a combined phase 3 product will perform, or whether heart disease or survival will change.